Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder selectively affecting motor neurons resulting in progressive weakness. Currently there is no known cure and a specific etiology has not been identified. Creatine is a nutritional supplement that improves mitochondrial function and has been shown to protect motor neurons in animal models of ALS. Based on our preliminary results presented in this proposal, creatine may also improve strength in patients with ALS.The Specific Aims of this proposal are to: 1) Determine whether treatment with creatine results in an acute increase in muscle strength and whether that effect is sustained with chronic therapy. 2) Determine whether chronic treatment with creatine will slow the progressive deterioration of motor and pulmonary function in patients with ALS. 3) Determine whether administration of loading doses of creatine followed by chronic treatment is safe in patients with ALS.This will be a phase III, double-blind, placebo-controlled, multi-center safety and efficacy study of creatine in 100 patients with ALS treated for nine months. The primary outcome measures are changes in disease progression rate as measured by 1) the maximum voluntary isometric contraction (MVIC) strength of ten arm muscle groups (bilateral shoulder and elbow flexion-extension and grip strength and 2) manual muscle testing (MMT) of the same ten arm muscle groups. Secondary endpoints include the rate of decline of forced vital capacity (FVC, percent predicted), the change in the ALS functional rating scale (ALSFRS-R), the SF-12 (quality of life instrument), and the safety and tolerability of creatine.